HLA-DRB1 and HLA-DQB1 genes on susceptibility to and protection from allergic bronchopulmonary aspergillosis in patients with cystic fibrosis

• Published in: Microbiology and immunology Vol. 57; no. 3; p. 193
• Main Authors: Muro, Manuel, Mondejar-López, Pedro, Moya-Quiles, María Rosa, Salgado, Gema, Pastor-Vivero, María Dolores, Lopez-Hernandez, Ruth, Boix, Francisco, Campillo, José Antonio, Minguela, Alfredo, Garcia-Alonso, Ana, Sánchez-Solís, Manuel, Álvarez-López, María Rocío
• Format: Journal Article
• Language: English
• Published: Australia 01.03.2013
• Subjects: Aspergillosis, Allergic Bronchopulmonary - genetics; Cystic Fibrosis - complications; Gene Frequency; Genetic Predisposition to Disease; Genotype; HLA-DQ beta-Chains - genetics; HLA-DRB1 Chains - genetics; Humans; Polymerase Chain Reaction
• ISSN: 1348-0421; 0385-5600; 1348-0421
• DOI: 10.1111/1348-0421.12020

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity pulmonary disease that affects both patients with cystic fibrosis (CF) and those with asthma. HLA-DRB1 alleles have previously been associated with ABPA-CF susceptibility; however, HLA-DQB1 allele associations have not been clearly established. The aim of the present study was to investigate HLA class II associations in patients with ABPA-CF and determine their roles in susceptibility or protection. Patients with ABPA-CF, patients with CF without ABPA, patients with asthma without ABPA (AST), and healthy controls were included in this study. DNA was extracted by automatic extractor. HLA-DRB1 and -DQB1 genotyping was performed by the Luminex PCR-SSOP method (One Lambda, Canoga Park, CA, USA). Allele specific PCR-SSP was also performed by high-resolution analysis (One Lambda). Statistical analysis was performed with SSPS and Arlequin software. Both HLA-DRB1*5:01 and -DRB1*11:04 alleles occurred with greater frequency in patients with ABPA-CF than in those with AST and CF and control subjects, corroborating previously published data. On the other hand, analysis of haplotypes revealed that almost all patients with ABPA-CF lacking DRB1*15:01 or DRB1*11:04 carry either DRB1*04, DRB1*11:01, or DRB1*07:01 alleles. In the HLA-DQB1 region, the HLA-DQB1*06:02 allele occurred more frequently in patients with ABPA-CF than in those with AST and CF and healthy controls, whereas HLA-DQB1*02:01 occurred less frequently in patients with ABPA-CF. These data confirm that there is a correlation between HLA-DRB1*15:01, -DRB1*11:04, DRB1*11:01, -DRB1*04 and -DRB1*07:01 alleles and ABPA-CF susceptibility and suggest that HLA-DQB1*02:01 is an ABPA-CF resistance allele.